A Risky Drug Approval Lesson

What the FDA can learn from progress against muscular dystrophy.

By The Editorial Board

Some welcome news arrived recently for boys with a condition called Duchenne muscular dystrophy. A new therapy is showing promising results, and it raises a question for the Food and Drug Administration: What if society had missed this moment?

In late June Sarepta Therapeutics , a biotech company, released data on a gene therapy for Duchenne, a disease that weakens muscles and organ function. Patients tend to die before age 25. The therapy is still very early in the pipeline and the data are from only three patients, but the details are striking.

View of human skeletal muscle under a microscope.
View of human skeletal muscle under a microscope. PHOTO: ISTOCK/GETTY IMAGES

The hallmark of Duchenne is the absence of dystrophin, a protein in skeletal muscle. Yet three months after treatment with the new therapy patients appear to be producing functional versions of the stuff. Biopsies showed on average 38.2% of normal levels. If that sounds modest, boys with 10% or even 5% of normal levels have a much more mild dystrophy known as Becker.

The treatment also showed a sharp reduction in an enzyme associated with muscle decay. No one knows how the disease will progress in these young boys, but it could be a radical departure from the norm.

Yet a mere two years ago Sarepta almost folded as it worked to win FDA approval for a drug known then as eteplirsen, now marketed as Exondys 51. Reviewers complained that the drug didn’t produce enough dystrophin, and that the company’s clinical trial was too small, among other objections.

FDA approved the drug after a long and ugly fight within the agency, and that decision was right on the merits. Eteplirsen was an improvement over available treatments, of which there were none. On the evidence so far the drug is slowing decline in patients.

But if FDA had cashiered that therapy, Sarepta would have lacked the resources to continue its research and testing to treat Duchenne and develop what may be an even better drug. If eteplirsen had failed to get approval, dollars and brain power would inevitably have flowed toward treating other diseases with more promise of success. FDA has tremendous influence over private investment.

Risk-averse FDA reviewers have traditionally focused on avoiding what the agency knows as a Type I error: Approving a drug that isn’t safe or effective. A potential breakthrough on Duchenne is a reminder that a Type II error—rejecting a drug that should have been approved—carries risks beyond one drug. That failure can delay innovations and perhaps cures.

Sarepta’s gene therapy is hardly a sure bet, and the company’s competition may come up with something better. But FDA Commissioner Scott Gottlieb has written on these pages that the agency’s culture must adapt to tolerate uncertainty, especially in diseases with few or no approved treatments. Dr. Gottlieb’s legacy will depend in large part on how much he can change that culture.

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